Liposomes Containing Zinc-Based Chemotherapeutic Drug Block Proliferation and Trigger Apoptosis in Breast Cancer Cells.
Mallayasamy SivaKiran DasSubhabrata GuhaSubramaniyam SivagnanamGaurav DasAbhijit SahaAdele StewartBiswanath MaityPriyadip DasPublished in: ACS applied bio materials (2023)
Platinum-based chemotherapeutic drugs are effective in killing malignant cells but often trigger drug resistance or off-target side effects. Unlike platinum, zinc is used as an endogenous cofactor for several cellular enzymes and may, thus, display increased biocompatibility. In this present study, we have rationally designed and synthesized two substituted phenanthro[9,10- d ]imidazole-based ligands L1 and L2 with pyridine and quinoline substitution at the 2 position and their corresponding Zn(II) complexes; (L1) 2 Zn and (L2) 2 Zn , which are characterized by standard analytical and spectroscopic methods. (L2) 2 Zn , but not (L1) 2 Zn has intrinsic fluorescence, indicating its potential utility in imaging applications. To facilitate cellular uptake, we generated liposomal formations with a phospholipid DMPC (1,2-Dimyristoyl- sn -glycero-3-phosphocholine) through molecular self-assembly. These liposomal formulations Lip-(L1) 2 Zn and Lip-(L2) 2 Zn were able to enter breast cancer cells, induce DNA fragmentation, arrest the cell cycle at the G0/G1 phase, decrease proliferation, and promote apoptosis by activating the DNA damage response. Importantly, both Lip-(L1) 2 Zn and Lip-(L2) 2 Zn decreased the size of breast cancer cell-based spheroids, indicating they may be capable of suppressing tumor growth. Our work represents an important proof-of-concept exercise demonstrating that successful liposomal formation of phenanthro[9,10-d]imidazole-based Zn(II) complexes with inherent optical properties have great promise for the development of imaging probes and efficient anticancer drugs.
Keyphrases
- heavy metals
- cell cycle
- breast cancer cells
- signaling pathway
- cell cycle arrest
- oxidative stress
- dna damage response
- high resolution
- cell proliferation
- single molecule
- cell death
- induced apoptosis
- emergency department
- mass spectrometry
- high intensity
- deep learning
- photodynamic therapy
- machine learning
- dna damage
- liquid chromatography
- living cells
- fatty acid
- drug induced
- fluorescent probe
- drug release